Nitrosamines have the following molecular structure: ##STR1## in which R.sub.1 and R.sub.2 represent organic (carbon-containing) groups. In precise chemical terminology, R.sub.1 and R.sub.2 should represent alkyl or aryl groups, but not carbonyl groups which have C-O double bonds. If either of the alpha carbons (the carbons attached directly to the nitrogen) in a nitrosamine molecule is double-bonded to an oxygen atom, the molecule should properly be called a "nitroso-" compound (such as nitrosoamide, nitroso-carbamate, nitrosourea, etc.). However, the carbonyl/nitroso distinction is often disregarded in toxicological and medical research and in government and mass-media publications, because many nitroso compounds are carcinogens and generate the same public concerns as nitrosamines. Since the subject invention relates to methods and compounds for eliminating or reducing carcinogens, the term "nitrosamine" as used herein includes nitroso compounds.
Some types of nitrosamines have been shown to be carcinogenic in tests using laboratory animals. In general, all nitrosamines are presumed to be carcinogenic unless they've been tested and shown to be relatively harmless; for example, nitrosamines with tertiary butyl or two benzyl groups attached to the nitrogen reportedly are not carcinogenic in test animals.
Nitrosamines are often generated as undesired byproducts in certain foods (especially bacon) and cosmetic and hygiene products (such as shampoo and hair conditioner). Nitrosamines are also present in various other fluids that can come into contact with the skin, such as metal-working fluids (which are used to cool and/or lubricate metal pieces during machining processes), hydraulic fluids, and in pesticides and various other commercial chemicals.
In addition, nitrosamines can be generated during the manufacturing or molding of rubber. Such nitrosamines are often released into the air, creating workplace and environmental hazards due to carcinogenic air pollution.
Nitrosamine contaminants usually result from the reaction of nitrosating agents with amines. The primary nitrosating agents are formed from the dissolution of nitrite salts, such as sodium or potassium nitrite, in acids, and the resulting mixture is often referred to as nitrous acid (HNO.sub.2). In addition to nitrous acid, the other nitrosating agents contained within this mixture also may include nitrosyl halides, nitrosyl sulfuric acid, nitrous anhydride (N.sub.2 O.sub.3), dinitrogentetroxide (N.sub.2 O.sub.4), or nitrosyl thiocyanate, depending upon which acid is used to generate the nitrous acid and what other salts may be present. Nitrosating agents such as N.sub.2 O.sub.3 and N.sub.2 O.sub.4 can also form in the absence of acid and nitrite salts. They are, for example common constituents of polluted air and may form through the oxidation of NO. Nitrous esters (alkyl or aryl nitrites) of alcohols, phenols, or thiols are also nitrosating agents as are certain transition metal complexes of nitrite and NO. Nitrosation can occur during product preparation, either during heating or at moderate temperatures. It can also occur while a product sits on a shelf, especially if the product sits for months in a warehouse that becomes quite warm.
Many efforts have been made to eliminate nitrosamines from various substances, or to reduce their concentrations to the lowest practical levels. In various types of food, people and companies have used ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) and their salts to inhibit nitrosamine formation; e.g., U.S. Pat. Nos. 4,463,026 (Chendler et al 1984), 4,434,187 (Chendler et al 1984), and 4,251,563 (Czuba et al 1981). Others have used acetal and ketal derivatives of ascorbic acid (U.S. Pat. No. 4,153,613, Bharucha et al 1979). Others have used gamma-pyrone (U.S. Pat. No. 4,443,483, Sato et al, 1984). Others have used "reducing sugars," which generally comprise sugar derivatives with attached alkyl groups, such as methyl-glucoside (e.g., U.S. Pat. No. 4,435,433, Theiler, 1984). Others have used mixtures where the exact chemical composition is either unknown or unspecified, such as "an aqueous extraction of black tea leaves" (U.S. Pat. No. 4,844,925, Mai et al 1989) or "liquid smoke" (e.g., U.S. Pat. Nos. 4,414,232, Rendek et al 1983, and 4,411,922, Theiler 1983).
In the field of topical products (i.e., products that contact the skin, such as cosmetics, shampoo, and hair conditioner), U.S. Pat. No. 4,189,465 (Rosenthal 1980) discusses the use of squalene, a complex biological hydrocarbon.
In the chemical industry, compounds such as sulfamic acid, ammonium sulfamate, ammonium sulfate, urea, mercaptans, and azides have been used (often under acidic conditions) to inhibit nitrosamine formation. In the petrochemical industry, U.S. Pat. No. 4,200,542 (Sedlak 1980) describes the use of metallic salts of ascorbate and isoascorbate with vitamin E to inhibit nitrosamine formation in grease compositions.
Various researchers have reported that certain types of "unsaturated" organic molecules (i.e., molecules with at least one double-bond) can be used to inhibit nitrosamine formation. Such compounds include hydrocarbons (which contain only carbon and hydrogen atoms), carbohydrates (which also contain oxygen), and heterocyclics (molecules which have a ring structure with at least one non-carbon atom in the ring, such as nitrogen or oxygen). For example, Gray and Dugan (1975) disclosed the use of hydroquinone as a nitrosamine inhibitor in food. Subsequently, U.S. Pat. No. 4,273,937 (Gum et al 1981) disclosed that 1,4-naphthoquinone and 1,4-naphthohydroquinone were more effective than hydroquinone and could be used at lower concentrations to achieve some degree of nitrosamine reduction; however, substantial quantities of nitrosamines were still generated under the conditions they used. U.S. Pat. Nos. 4,087,561 and 4,088,793 (both by Bharucha et al 1978) disclose the use of certain hydroquinoline derivatives (such as 6-alkoxy-1,2,3,4-tetrahydroquinoline) as nitrosamine inhibitors.
The foregoing methods of inhibiting nitrosamines suffer from various limitations and shortcomings. For example, ascorbic acid and alpha-tocopherol can react to produce NO, which can be oxidized by air to yield NO.sub.x, which can react with itself or NO to produce a nitrosating agent. Azides are highly toxic, while mercaptans have noxious odors. Ionic compounds (which includes salts that dissociate easily) are incompatible with many formulations, and some react more rapidly with other compounds than with nitrosating agents, which can lead to unwanted byproducts while the nitrosating agents remain as a threat to form nitrosamines.
Therefore, there remains a need for a general method of removing, sequestering, or otherwise inactivating nitrosating agents in fluid mixtures. Such a method should utilize a substance that reacts quickly with nitrosating agents, in a reaction that is not easily reversed, to form relatively stable compounds that (1) are not subsequently degraded or oxidized to form nitrosating agents or other undesired contaminants, or (2) can be easily removed from the mixture.